Catalysts

ABSTRACT

A tethered ligand comprising the reaction product of an organofunctional silica and a ligand containing a functional group capable of reaction with said organofunctional silica, wherein the organofunctional silica is prepared from an alkyl silicate and an organofunctional silane is described. A supported catalyst is also described comprising additionally a source of catalytically-active metal. Methods for preparing the tethered ligand and supported catalyst are provided and uses of the supported catalyst for performing asymmetric reactions are claimed. The catalysts are readily separable from the reaction mixtures and may be re-used if desired.

This invention relates to ligands tethered to solid supports and inparticular to ligands tethered to silica that provide a means forsupporting metal catalysts which are useful for directing chemicalreactions. The products of such reactions are useful, for example, aschemical intermediates or reagents for use in the production of finechemicals or pharmaceutical intermediates.

The fixing of homogeneous catalysts to solid supports provides thepotential for extending the benefits of heterogeneous catalysts tohomogeneous systems. These benefits include easier separation ofcatalyst and reaction products leading to shorter work up times andimproved process efficiency, the potential for re-activation and re-useof the supported catalysts which are often based on expensive metals andcomplex ligand geometry, and the possible adaptation of the immobilisedcatalyst to continuous flow fixed-bed processes.

Strategies for homogeneous catalyst immobilisation have been based onabsorption, ion exchange or tethering the catalysts to a support usingcovalent attachment. By covalent attachment we mean the formation of acovalent bond between support and catalyst. Covalent attachment isattractive for providing catalysts that may be more robust to catalystleaching and hence retain higher activities upon re-use. Covalentattachment of the metal catalyst may be achieved by forming chemicalbonds between a ligand and particles of a polymer, for examplepolystyrene, or oxide material, for example silica, that has beensubjected to a surface functionalisation.

For example, Jacobsen (J. Am. Chem. Soc. 1999, 121, 4147-4154) hasreported the covalent attachment of the ligand ‘salen’ to polystyreneand fine silica particles. The ligand was immobilised by functionalgroup interconversion to add a linking molecule with a siloxy group atthe end. The ligand was then grafted onto 10 μm spherical silicaparticles and used for the hydrolytic kinetic resolution of a variety ofterminal epoxides. Kim et al (Catalysis Today. 2000, 63, 537-547)described confining a chiral catalyst on an alkyl silicate-derivedsilica-MCM-41 by a multi-step process including surface treating thesilica material with 3-aminopropyl trimethoxysilane to activate thesilica prior to reaction with a precursor of the required chiralcatalyst and then further treatment to produce the immobilised catalyst.

These methods for providing covalent attachment of ligand and catalystdepend upon the surface activity of the silica material being subjectedto treatment Variations in the silica material may result in catalystswith lower enantioselectivities and/or efficiencies than the homogeneouscounterpart. Furthermore, the practical advantages gained by covalentattachment to a support are often outweighed by the added complexityassociated with synthesising the appropriately modified support and/orchiral ligand.

Improved consistency in functionalised silicas is required. Clarke andMacquarrie (Chem. Commun., 1998, 2707-2708) describe a method forgenerating a silica-supported peroxycarboxylic acid for the epoxidationof alkenes wherein the silica is prepared via a co-hydrolysis oftetraethylorthosilicate and 2-cyanoethyltriethoxysilane. However, theresulting peroxyacid is not suitable for tethering homogeneouscatalysts.

We have now found that homogeneous catalysts may be successfullyimmobilised using functionalised silicas prepared from alkyl silicatesand organofunctional silanes.

According to the invention we provide a tethered ligand comprising thereaction product of an organofunctional silica and a ligand containing afunctional group capable of reaction with said organofunctional silica,wherein the organofunctional silica is prepared from an alkyl silicateand an organofunctional silane.

According to a further aspect of the invention we provide a supportedcatalyst comprising the reaction product of an organofunctional silica,a ligand containing a functional group capable of reaction with saidorganofunctional silica and a source of catalytically-active metal,wherein the organofunctional silica is prepared from an alkyl silicateand an organofunctional silane.

According to a further aspect of the invention, we also provide a methodfor the preparation a tethered ligand comprising the steps of;

-   -   a) forming an organofunctional silica by the reaction of an        alkyl silicate, an organofunctional silane and water, optionally        in the presence of a template compound,    -   b) removing the template compound if present, and    -   c) reacting said organofunctional silica with a ligand        containing a functional group capable of reaction with said        organofunctional silica.

According to a further aspect of the invention, we also provide a methodfor the preparation of a supported catalyst comprising the steps of;

-   -   a) forming an organofunctional silica by reaction of an alkyl        silicate, an organofunctional silane and water, optionally in        the presence of a template compound,    -   b) removing the template compound if present,    -   c) reacting said organofunctional silica with a ligand        containing a functional group capable of reaction with said        organofunctional silica to produce a tethered ligand and    -   d) carrying out a chemical reaction between a metal compound and        said tethered ligand.

According to a further aspect of the invention, we also provide the useof a supported catalyst comprising the reaction product of anorganofunctional silica, a ligand containing a functional group capableof reaction with said organofunctional silica and a source ofcatalytically-active metal, wherein the organofunctional silica isprepared from an alkyl silicate and an organofunctional silane, forhydrogenation reactions, dihydroxylation reactions, hydrolysisreactions, metathesis reactions, carbon-carbon bond formation reactions,hydroamination reactions, epoxidations, aziridinations, cycloadditions,hetero-Diels-Alder reactions, hetero-ene reactions, Claisenrearrangements, carbonyl reductions, sigmatropic rearrangements,additions of nucleophiles to π-bonds, addition of nucleophiles tocarbonyl groups and ring-opening reactions.

The present invention relates to tethered ligands. By the term ‘tetheredligand’ we mean an organic ligand covalently bound to a solid silicasupport. By the term ‘ligand’ we mean any molecule capable of reactingwith a metal compound to produce a catalyst

Organofunctional silicas of the present invention are prepared fromalkyl silicates and organofunctional silanes. The alkyl silicates aretetraalkylsilicates which have the general formula Si(OR)₄ in which eachR may be the same or different and is an alkyl group or substitutedalkyl group having between 1 and 4 carbon atoms. Alkyl silicates usefulfor the present invention include tetramethylorthosilicate,tetraethylorthosilicate and tetrapropylorthosilicate or mixtures ofthese. Preferably, the alkyl silicate is tetraethylorthosilicate ortetramethylorthosilicate.

The organofunctional silane of the present invention may be halo oralkoxy organofunctional silane according to the general formula(Y)_(a)Si((Z)X)_(b) in which;

-   Y is a halogen or alkoxy group having 1 to 3 carbon atoms;-   Z is an alkyl, aryl or alkyl-aryl group which optionally contains at    least one heteroatom selected from oxygen, nitrogen, phosphorus or    sulphur; and-   X is a functional group selected from halide, hydroxyl, carbonyl,    carboxyl, anhydride, carbene, methacryl, epoxide, vinyl, nitrile,    mercapto, amine, imine, amide and imide;-   a=3 or 2, b=1 or 2 and a+b=4.

In the above formula, if Z contains an alkyl group it preferably hasbetween 1 and 16 carbon atoms, is branched or linear and saturated orunsaturated. If Z contains an aryl group it is preferably a substitutedor unsubstituted phenyl, phenoxy or anilide moiety. Where X is bound toan alkyl group it may be bound on either a primary, secondary ortertiary carbon.

The organofunctional silane may be selected from those commerciallyavailable or if desired may be prepared by reaction of anorganofunctional silane with a linker molecule that provides afunctional group capable of reaction with a functional group-containingligand. The linker molecule may be any that contains a functional groupthat is capable of reacting with the organofunctional silane andprovides a suitable functional group in the resultant silica materialcapable of reacting with a functional group-containing ligand. Suitablelinker molecules include C1-C10 alkyl, alkoxy, alkyl-aryl, aryl, phenoxyor anilide compounds containing functional groups selected from halide,hydroxyl, carbonyl, carboxyl, anhydride, carbene, methacryl, epoxide,vinyl, nitrile, mercapto, isocyanate, amine, imine, amide and imide.Advantages of preparing the organofunctional silane in this way are thatnew functional groups may be introduced in a way that is not generallypossible in commercially available silanes, functional groups may beintroduced at a greater distance from the silicon atom than is possiblewith currently available silanes, and such modification may provideorganofunctional silanes that provide improvements in the properties ofthe resulting organofunctional silica, e.g. porosity.

Mixtures of organofunctional silanes having different functional groupsmay be used in the present invention. In such mixtures 2 or more silanesmay be present.

Optionally, a silane not having a functional group capable of reactionwith a functional group-containing ligand may be used In combinationwith an organofunctional silane as described above to e.g. reduce thesurface concentration of functional groups on the silica material andimprove ligand attachment. Such non-functionalised silanes may also beused to improve other properties of the resulting silica material suchas porosity or pore size. Typically silanes such as alkyl silanes can beused although other non-functionalised silanes may also be used. Themolecular ratio of functionalised and non-functionalised silanes usedmay be any that provides a sufficient number of reactive sites fortethering the ligand containing a functional group to the resultingorganofunctional silica to provide a useful level of catalytic activityin the final catalyst. Molecular ratios may be in the range 1:99 to 99:1for any given pair of silanes, preferably 1:9 to 9:1.

Organofunctional silanes useful for the present invention includevinyltrimethoxy silane, vinyltriethoxysilane, dichlorodivinylsilane,3-(aminopropyl)trimethoxysilane, 3-(aminopropyl)triethoxysilane,[3-(methacryloyloxy)-propyl]trimethoxysilane,[3-[tri(ethoxy/methoxy)silyl]propyl]urea,3-(glycidoxypropyl)trimethoxysilane, 4-(triethoxysilyl)butyronitrile,3-(lodopropyl)trimethoxysilane, 3-(mercaptopropyl)-trimethoxysilane,3-(triethoxysilyl)propionitrile, 4-(triethoxysilyl)butyronitrile,((chloromethyl)-phenylethyl)trimethoxysilane, and((chloromethyl)phenyl)trimethoxysilane and mixtures of these.

Non-functionalised silanes useful for the present invention includealkyl silanes having 1 to 16 carbon atoms such aspropyltrimethoxysilane, propyltriethoxysilane, butyltrimethoxysilane,hexylbutyltrichlorosilane, dodecyltrichlorosilane,octadecyltrimethoxysilane, octyltrimethoxysilane, octyltriethoxysilaneand mixtures of these.

The ligand containing a functional group suitable for reaction with theorganofunctional silica may be a chiral or non-chiral mono-, bi-, tri-or tetra-dentate ligand. If a chiral ligand is used it may be a racemicor non-racemic mixture or single enantiomer having a reactive groupcapable of reacting with the organofunctional silica. Typically suchligands include β-diketonates, β-ketoesters, alkanolamines, Schiffbases, aminoacids, peptides, phosphates, phosphites, alkyl- oraryl-phosphines, diamines, crown-ethers and bis-oxazolines. Preferredligands containing a functional group are chiral ligands and include,but are not limited to racemic and non-racemic mixtures or singleenantiomers of bidentate ligands such as;

The functional groups to be reacted with the organofunctional silica mayconveniently be introduced into the ligand during its preparation. If afunctional group available on the ligand is unsuitable for reaction withthe organofunctional silica, it may be converted by chemical reaction oralternatively, the ligand may be reacted with a linker molecule thatprovides a suitable functional group capable of reaction with theorganofunctional silica. Suitable functional groups on the ligandinclude halide, hydroxyl, carbonyl, carboxyl, anhydride, carbene,methacryl, epoxide, vinyl, nitrile, mercapto, amine, imine, amide andimide.

The catalytically-active metal to be reacted with the ligand tethered tothe organofunctional silica is selected from the group comprising Sc,Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Tc, Re, Fe, Ru, Co, Rh, Ir, Ni,Pd, Pt, Cu, Ag, Al, Ge, Sb and Sn. Preferably, for asymmetrichydrogenation, the metal is selected from Rh, Ir or Ru; preferably forhydrolytic kinetic resolution of epoxides the metal is selected from Co;preferably for ring-opening reactions the metal is selected from Cr andAl; and preferably for Heck reactions the metal is Pd. The source of themetal may be any suitable for reaction with the ligand tethered to theorganofunctional silica. Preferably the source of the metal is anorganic complex of the metal or a metal salt. For example rhodium may bereacted as a 1,5-cyclooctadiene complex and for manganese, palladium orcobalt the metal may be reacted as the di-acetate.

A method for preparing an organfunctional silica by the co-hydrolysis ofan alkyl silicate and an organofunctional silane is depicted below. Thewavy line represents the silicon atom on or within the resulting silicamaterial.

In one embodiment, alkyl silicate and organofunctional silane are addedto a mechanically stirred mixture of solvent and water. The alkylsilicate and organofunctional silane may be added together, sequentiallyin any order or in alternating portions. In an alternative embodimentthe alkyl silicate, organofunctional silane and solvent are added to themechanically stirred water and in yet a further embodiment the alkylsilicate and organofunctional silane without solvent are added to themechanically stirred water. The alkyl silicate and organofunctionalsilane are added at a molecular ratio of greater than or equal to 1:1(silicate:silane). Preferably the ratio of alkyl silicate to silane isbetween 1:1 and 99:1 and more preferably between 1:1 and 10:1. Typicallythe solvent, if used, is an alcohol but may be any other solventsuitable for performing the co-hydrolysis reaction. For example, thesolvent may be methanol, ethanol or propanol. Water is present insufficient quantity to cause complete hydrolysis of the alkoxidemoieties on the alkyl silicate and is generally added in large excess.

A template compound may be added to the hydrolysis mixture to influencethe resulting pore structure and potentially the disposition of theorganofunctionality within the pores of the resulting organofunctionalsilica. Depending upon the method used, the template may be added to forexample, the solvent/water mixture, the alkyl silicate/organofunctionalsilane/solvent mixture or the alkyl silicate/organofunctional silanemixture. The templates function by becoming entrapped in the silica asit forms during the co-hydrolysis of the alkyl silicate andorganofunctional silane. Once the co-hydrolysis is complete, theentrapped template may then be removed by, for example, solventextraction to leave behind pores corresponding to the structure of thetemplate molecule. Suitable solvents for solvent extraction includealcohols, e.g. ethanol. Template compounds may be used in thepreparation of mico- and meso-porous silicas (where a micro-poroussilica has an average pore width of less than 20 Å and a meso-poroussilica has an average pore width of between 20 and 500 Å). Preferablythe organofunctional silica of the present invention is a meso-poroussilica having an average pore width, as measured by BET porosimetry, ofbetween 20 and 500 Å.

Template compounds include amines, quaternary ammonium salts andnon-ionic poly(ethylene oxide)/(propylene oxide) surfactants such asamphilic block copolymers. Suitable amphilic block copolymers aretri-block copolymers, e.g. PLURONIC™ F127 (EO₁₀₆PO₇₀EO₁₀₆) and PLURONIC™123 (EO₂₀PO₇₀EO₂₀) and mixtures of these. The quaternary ammoniumcompounds are quaternary ammonium salts or hydroxides e.g. of generalformula [R₄N]⁺[Z]⁻ in which R may be the same or different and is alkylor substituted alkyl (C1-C30), and Z is preferably Cl, Br, or OH.Quaternary ammonium compounds wherein the nitrogen atom forms part of aring structure may also be used. Suitable quaternary ammonium compoundsare tetrapropylammonium hydroxide, tetrapropylammonium chloride,tetrabutylammonium hydroxide, benzyltrimethylammonium hydroxide,benzylcetyldimethylammonium chloride, benzyltrimethylammonium hydroxide,benzyltrimethylammonium chloride, cetyltrimethyl ammonium hydroxide,cetyltrimethylammonium bromide, cetyltrimethylammonium chloride andmixtures of these. Preferably the template molecule is an amine.Suitable amines are amines having 10 or more carbon atoms in thestructure and preferably are C12 to C18 alkyl amines such asn-dodecylamine or n-octadecylamine or mixtures of these. The amount oftemplate compound required will depend upon a number of factorsincluding the amount of alkyl silicate used. In general the relativeamounts of template molecule may vary in the range 1:10 to 50:1 andpreferably in the range 1:1 to 10:1 parts by weight silicate:templatecompound.

In addition to the template, a pore-enlarging additive may be includedin the hydrolysis mixture. A known pore-enlarging additive is mesitylene(1,3,5-trimethylbenzene). Depending upon the method chosen forperforming the co-hydrolysis reaction, the pore swelling additive mayfor example, be combined with the silicate and organofunctional silaneor with the water or water/solvent mixture or may be added separately tothe hydrolysis mixture. The amount of pore-enlarging additive that maybe added will depend upon the properties of the additive, for example inthe present invention 1-2 moles of mesitylene may be added per mole ofalkyl silicate.

The co-hydrolysis reaction may be performed at room temperature or ifdesired at elevated temperature depending on the physical properties ofthe solvent chosen. For example the co-hydrolysis reaction may becarried out at between 10-50° C. for periods between 1 and 36 hours.When the co-hydrolysis reaction is complete the organofunctional silicais recovered by, for example filtration and the template, if present,removed by solvent extraction. Solvent extraction may be effected forexample by heating the re-suspended organofunctional silica in asuitable solvent such as ethanol. This may be repeated as necessary toremove all of the template prior to attachment of the functionalgroup-containing ligand.

It may be desirable to change the functional groups present on theorganofunctional silica to, for example, provide a different functionalgroup with which to react the functional group containing-ligand. Forexample, if the functional group containing-ligand has a pendanthydroxyl group capable of reaction with the organofunctional silica, itmay be desirable to chemically convert the functional group on thesilica from, for example a cyano-group to a carboxyl group or, acarboxyl group to an acid-chloride group, to facilitate a reactionbetween said silica and said ligand. Such conversions may also provide ameans for providing functional groups on the silica not practical as aresult of the method used for preparing the organofunctional silica. Forexample, isocyanate groups that would be unstable to the water usedduring the co-hydrolysis of alkyl silicate and organofunctional silanemay be provided by inter-conversion of acid-chloride via a Curtisrearrangement Alternatively, a chemical conversion may be performed toreduce the surface concentration of functional groups capable ofreaction with the functional group-containing ligand by, for example,converting the functional groups to unreactive species such as hydrogenor alkyl groups.

Alternatively the organofunctional silica may be reacted with a linkermolecule that provides a functional group capable of reaction with afunctional group-containing ligand, to form a new organofunctionalsilica. This may be of particular use where chemical conversion offunctional groups is difficult. The linker molecule may be any that iscapable or reacting with the organofunctional silica and provides asuitable functional group for reacting with the ligand. Suitable linkermolecules include C1-C10 alkyl, alkoxy, alkyl-aryl, aryl, phenoxy oranilide compounds containing functional groups selected from halide,hydroxyl, carbonyl, carboxyl, anhydride, carbene, methacryl, epoxide,vinyl, nitrile, mercapto, isocyanate, amine, imine, amide and imide.Suitable linker molecules include (3-Formylindol-1-yl)acetic acid,[3-({Ethyl-Fmoc-amino}-methyl)-indol-1-yl]-acetic acid,2,4-Dimethoxy-4′-hydroxy-benzophenone, 3,5-Dimethoxy-4-formyl-phenol,3-(4-Hydroxymethylphenoxy)propionic acid, 3-Carboxypropanesulfonamide,3-Hydroxy-xanthen-9-one, 3-Methoxy-4-formylphenol,4-(2-Bromopropionyl)phenoxyacetic acid,4-(4-[Bis-(4chlorophenyl)hydroxymethyl]phenoxy)butyric aciddicyclohexylammonium salt, 4-(4-Formyl-3-methoxy-phenoxy)-butyric acid,4-(4-Hydroxymethyl-3-methoxyphenoxy)-butyric acid,4-[4-(1-(Fmocamino)ethyl)-2-methoxy-5-nitrophenoxy)butanoic acid,4-[4-(1-Hydroxyethyl)-2-methoxy-5-nitrophenoxy)butanoic acid,4-[4-(2,4-Dimethoxybenzoyl)phenoxy]butyric acid,4-[4-(Diphenylhydroxymethyl)phenoxy]butyric acid dicyclohexylammoniumsalt, 4-[4-Hydroxymethyl-2-methoxy-5-nitrophenoxy)butanoic acid,4-Hydroxy-2,6-dimethoxy-benzaldehyde, 4-Hydroxy-2-methoxy-benzaldehyde,4-Hydroxymethylbenzoic acid, 4-Hydroxymethylphenoxyacetic acid,4-Sulfamoyl-butyric acid andp-[(R,S)-α-[1-(9H-Fluoren-9-yl)-methoxyformamido]-2,4-dimethoxybenzyl]-phenoxyaceticacid

A reaction of a ligand containing a functional group with anorganofunctional silica to provide a tethered ligand is depicted below.Y represents the functional group on the ligand capable of reaction withthe organofunctional silica and A represents the covalent bond betweenligand and organofunctional silica;

The reaction may be achieved by any effective chemical reaction betweenthe functional groups of the organofunctional silica and the functionalgroup containing-ligand. Typical reactions include for example,esterification reactions, amidation reactions, addition reactions,substitution reactions, insertion reactions and carbon-carbon couplingreactions and may be performed by any method known to those skilled inthe art. For example, esterification reactions may be performed betweenligand and silica either having carboxyl and hydroxyl groups, anhydrideand hydroxyl groups or acid-chloride and hydroxyl groups in the presenceof suitable catalysts or reagents. Amidation reactions may be performedbetween ligand and silica either having carboxyl groups and primary orsecondary amine groups or anhydride groups and primary or secondaryamine, again in the presence of suitable catalysts or reagents.

A reaction of a metal with a tethered ligand to provide a supportedcatalyst is depicted below;

The reaction may be achieved by methods known to those skilled in theart and is preferably effected by reaction of a metal compound with thetethered ligand. Such reactions include, for example, ligandsubstitution reactions and metal-insertion reactions. The metal mayalso, if desired, be subjected to steps of oxidation or reduction toprovide the necessary catalytic activity. For example cobalt catalystsmay be oxidised from Co(II) to Co(III) or rhodium catalysts may bereduced from Rh(III) to Rh(I).

Preferably the tethered ligands of the present invention are chiralligands providing supported chiral catalysts. The supported chiralcatalysts of the present invention may be applied to a large number ofasymmetric reactions used to produce chiral products. Such reactionsinclude hydrogenation reactions, dihydroxylation reactions, hydrolysisreactions, metathesis reactions, carbon-carbon bond formation reactionssuch as Heck or Suzuki reactions, hydroamination reactions,epoxidations, aziridinations, cycloadditions, hetero-Diels-Alderreactions, hetero-ene reactions, Claisen rearrangements, carbonylreductions, sigmatropic rearrangements, additions of nucleophiles toπ-bonds, addition of nucleophiles to carbonyl groups and ring-openingreactions. Preferably the reactions are hydrogenation reactions,hydrolysis reactions and carbon-carbon bond formation reactions. Theadvantages of the catalysts of the present invention are that they arereadily separated from the reaction products and may be re-used if sodesired.

The invention is illustrated by the following examples.

EXAMPLE 1 Preparation of Catalyst A

(a) Preparation of Mesoporous Carboxylic Acid-Functionalised Silica

A mixture of ethanol (105 ml), de-ionised water (105 ml) andn-dodecylamine (10 g) was prepared and stirred vigorously at roomtemperature until homogeneous. To this mixture, tetraethylorthosilicate(20.4 g) and 3-(triethyoxysilyl)propionitrile (23.1 g) were addedstepwise over 30 minutes with continued stirring for 24 hours. Afterthis time the precipitate was filtered, washed with de-ionised water(500 ml) and ethanol (500 ml) then allowed to dry at room temperaturefor 24 hours. Extraction of n-dodecylamine was achieved by heating thesolid at reflux in ethanol (200 ml) for 3 hours. This reflux wasrepeated three times. The solid was then filtered and dried in a vacuumoven at 80° C. overnight. Hydrolysis of the nitrile functionality wasachieved by heating the solid to 120° C. in 50% v/v aqueous sulphuricacid (150 ml per 5 g) for 3 hours. The solid was filtered and washedwith excess de-ionised water until natural pH was achieved before dryingin a vacuum oven at 80° C. overnight. BET porosimetry analysis of thesilica indicated that it had an average pore width of 40 Å.

(b) Tethering of Ligand

To a stirred suspension of the mesoporous carboxylic acid functionalisedsilica (0.1 g), bppm (0.05 g, 0.11 mmol) and 4-dimethylaminopyridine(DMAP) (3.0 mg,) in dichloromethane (2.5 ml) was addeddiisopropylcarbodiimide (DIC) (17 μl, 0.11 mmol). The resultingsuspension was stirred overnight at room temperature. The mixture wasfiltered and the resulting solid washed with dichloromethane (5 ml),methanol (5 ml) and dichloromethane (5 ml). The solid was dried undervacuum to give the ligand supported Silica as a colourless solid.

(c) Insertion of Metal

A mixture of the ligand supported silica (0.1 g) and [Rh(cod)₂]BF₄ (44mg, 0.1 mmol) in dichloromethane (2.5 ml) was stirred for 1 hr undernitrogen. The mixture was then filtered and the solid washed withdichloromethane (2.5 ml), methanol (5 ml) and dichloromethane (2.5 ml).The solid was dried under vacuum to give the Rh-ligand supported silicaas a yellow solid. The tethering of ligand (I) and insertion of metal(II) may be depicted as follows;

EXAMPLE 2 Hydrogenation of Dimethylitaconate

Dimethylitaconate was hydrogenated according to the following scheme;

Dimethylitaconate substrate and catalyst were weighed into a glass-linerthat was placed inside a 50 ml autoclave to give a substrate:catalystmolar ratio of 100:1. The autoclave was sealed and flushed withnitrogen. The autoclave was then pressurised with hydrogen to 80 psi(506.6 kPa) and then released (cycle repeated 5 times). Sufficientmethanol was added to the autoclave to give an approximately 1M solutionand the 5 cycles of pressurising-releasing with hydrogen were repeated.Finally the autoclave was pressurised with H₂ to 80 psi (506.6 kPa) andleft to stir. After the desired time the stirring was stopped and the H₂released slowly. The autoclave was opened and the mixture filtered torecover the supported catalyst. Gas-chromatographic analysis of thefiltrate was performed to determine conversion and enantiomeric excess(ee %). The results are given below. Catalyst Conversion (%) ee (%)Catalyst A 100 17

The result demonstrates that highly active catalysts can be preparedaccording to the present invention, that provide a means for producingchiral products and which are easily separated from the reactionmixture.

EXAMPLE 3 Preparation of Tethered Ferrocenyl Ligand

An organofunctional silica prepared according to the method of example 1part (a) was reacted with a ferrocenyl-bis(phosphine) ligand accordingto the following scheme;

An oven dried Schlenk tube was charged under nitrogen withcarboxy-functional silica prepared according to the method of example 1part (a) (0.213 g, 0.64 mmol; approx. 3 mmol/g loading) and drydichloromethane (3 ml). 1,1′-Carbonyldiimidazole (0.104 g, 0.64 mmol)was added, and the mixture was stirred until the bubbling ceased(approx. 15 min). The phosphine 1 (0.185 g, 0.32 mmol) was addedfollowed by dry dichloromethane (1 ml). After stirring for 20 hours atroom temperature under nitrogen, methanol (10 ml) was added, the mixturewas filtered, and the solid was washed with dichloromethane, methanol,and once more with dichloromethane. The resulting beige solid was driedunder high vacuum to give 0.202 g 2. ICP analysis: 0.52% Fe (w/w), 0.093mmol/g loading; 0.60% P (w/w), 0.097 mmol/g loading; the average loadingis therefore 0.095 mmol/g.

EXAMPLE 4 Heck Reaction Using a Supported Catalyst

A Heck reaction was performed using the tethered ligand of Example 3reacted with palladium acetate according to the following scheme;

An oven dried Schlenk flask was charged with Pd(OAc)₂ (2.2 mg, 0.01mmol, 1 mol %) and tethered ligand 2 (45.8 mg, 0.0044 mmol, 0.44 mol %).The flask was evacuated and backfilled with nitrogen and then cappedwith a rubber septum. Dry dimethylformamide (5 ml) was added and themixture was stirred for 60 min at room temperature under nitrogen.4′-Bromoacetophenone (0.199 g, 1.0 mmol), styrene (0.137 ml, 1.2 mmol),and triethylamine (0.195 ml, 1.4 mmol) were added successively. Therubber septum was replaced with a glas stopper, the flask was sealed,and the mixture was stirred at 120° C. for 20 h. After cooling to roomtemperature, the mixture was filtered, and the solid was washed withmethyl-t-butyl ether (MTBE), water, MeOH, acetone, and once more withMTBE. The phases of the filtrate were separated and the aqueous phasewas extracted with MTBE (2×30 ml). The combined organic extracts weredried over MgSO₄ and concentrated under reduced pressure. The crudeproduct was purified by flash chromatography on silica gel(hexane/EtOAc, 10/1 to 1/1) to give E-4-acetylstilbene (0.192 g, 86%) asa white solid.

EXAMPLE 5 Preparation of a Carboxylic Acid-Functionalised Silica Using aMixture of Functionalised and Non-Functionalised Silanes

A mixture of dodecylamine (10 g), deionised water (105 ml) and denatured(5% MeOH) ethanol (105 ml) was prepared and stirred for 30 minutes untilhomogeneous. To this, mesitylene (1 9.5 g) was added and the resultantcloudy emulsion was stirred for a further 30 minutes. After this time, afreshly prepared mixture of 4-triethoxysilylbutyronitrile (11.5 g) andpropyltrimethoxysilane (8.5 g) was added with continual stirring. Aftera further 60 minutes tetraethylorthosilicate (20.8 g) was added to themixture and the resultant slurry stirred for a period of 24 hours. Afterthis time the precipitate was filtered, washed with de-ionised water(500 ml) and ethanol (500 ml) then allowed to dry at room temperaturefor 24 hours. Template extraction and hydrolysis of the nitrilefunctionality were performed as described in Example 1 part (a) to yielda white solid having a nitrogen content of 3.6% by weight compared with7.2% by weight for the silica material prepared without thepropyltrimethoxysilane.

1. A tethered ligand comprising the reaction product of a meso-porousorganofunctional silica having an average pore width, as measured by BETporosimetry, of between 20 and 500 Angstroms and a ligand containing afunctional group capable of reaction with said organofunctional silica,wherein the organofunctional silica is prepared from an alkyl silicateand an organofunctional silence.
 2. A tethered ligand according to claim1, wherein the alkyl silicate has the general formula Si(OR)₄ in whicheach R may be the same or different and is an alkyl group or substitutedalkyl group having between 1 and 4 carbon atoms.
 3. A tethered ligandaccording to claim 1, wherein the organofunctional silane has thegeneral formula (Y)_(a)Si((Z)X)_(b) in which; Y is a halogen or alkoxygroup having 1 to 3 carbon atoms; Z is an alkyl, aryl or alkyl-arylgroup, which optionally contains at least one heteroatom selected fromoxygen, nitrogen, phosphorus or sulphur; X is a functional groupselected from halide, hydroxyl, carbonyl, carboxyl, anhydride, carbene,methacryl, epoxide, vinyl, nitrile, mercapto, amine, imine,. amide andimide; a=3 or 2, b=1 or 2 and a+b=4.
 4. A tethered ligand according toclaim 1, wherein the organofunctional silane is prepared by reaction ofan organofunctional silane with a linker molecule that contains afunctional group that is capable of reacting with the organofunctionalsilane and a functional group capable of reacting with a functionalgroup-containing ligand, said linker molecule selected from the groupcomprising C1-C10 alkyl, alkoxy, alkyl-aryl, aryl, phenoxy or anilidecompounds containing functional groups selected from halide, hydroxyl,carbonyl, carboxyl, anhydride, carbene, methacryl, epoxide, vinyl,nitrile, mercapto, isocyanate, amine, imine, amide and imide.
 5. Atethered ligand according to claim 1, wherein more than oneorganofunctional silane is used.
 6. A tethered ligand according to claim1, wherein the organofunctional silica is prepared from an alkylsilicate and an organofunctional silane and a silane not having afunctional group capable of reaction with a functional group-containingligand.
 7. A tethered ligand according to claim 1, wherein thefunctional group on the organofunctional silica is changed by chemicalconversion before reaction of the organofunctional silica with thefunctional group-containing ligand.
 8. A tethered ligand according toclaim 1, wherein the organofunctional silica is reacted with a linkermolecule that contains a functional group that is capable of reactingwith the organofunctional silica and a functional group capable ofreacting with a functional group-containing ligand.
 9. A tethered ligandaccording to claim 1, wherein the ligand containing a functional groupis a chiral or non-chiral mono-, bi-, tri- or tetra-dentate ligandhaving a reactive group capable of reacting with the organofunctionalsilica.
 10. A tethered ligand according to claim 9, wherein the ligandcontaining a functional group is a racemic or non-racemic mixture orsingle enantiomer of a β-diketonate, β-ketoester, alkanolamine, Schiffbase, aminoacid, peptide, phosphite, phosphate, alkyl- oraryl-phosphine, diamine, crown-ether and bis-oxazoline, each having areactive group selected from the group consisting of halide, hydroxyl,carbonyl, carboxyl, anhydride, carbene, methacryl, epoxide, vinyl,nitrile, mercapto, amine, imine, amide and imide.
 11. A method for thepreparation of a tethered ligand comprising the steps of; a) forming anorganofunctional silica by the reaction of an alkyl silicate, anorganofunctional silane and water, optionally in the presence of atemplate compound, b) removing the template compound if present, and c)reacting said organofunctional silica with a ligand containing afunctional group capable of reaction with said organofunctional silica.12. A method according to claim 11, wherein the functional group presenton the organofunctional silica formed in step (a) is changed by achemical conversion before reaction of the organofunctional silica withthe functional group-containing ligand.
 13. A method according to claim11, wherein the organofunctional silica formed in step (a) is reactedwith a linker molecule that contains a functional group that is capableof reacting with the organofunctional silica and a functional groupcapable of reaction with a function group-containing ligand.
 14. Amethod according to claim 11, wherein the molecular ratio of alkylsilicate to organofunctional silane is 1:1 to 99:1.
 15. A supportedcatalyst comprising the reaction product of a tethered ligand as claimedin claim 1 and a source of catalytically-active metal.
 16. A catalystaccording to claim 15, wherein the catalytically-active metal isselected from the group comprising Sc, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W,Mn, Tc, Re, Fe, Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Al, Ge, Sb and Sn.17. A catalyst according to claim 15, wherein the source ofcatalytically-active metal is an organic complex of the metal or metalsalt.
 18. A method for the preparation of a supported catalystcomprising the steps of; a) forming an organofunctional silica byreaction of an alkyl silicate, an organofunctional silane and water,optionally in the presence of a template compound, b) removing thetemplate compound if present. c) reacting said organofunctional silicawith a ligand containing a functional group capable of reaction withsaid organofunctional silica to produce a tethered ligand and d)carrying out a chemical reaction between a metal compound and saidtethered ligand.
 19. The use of a supported catalyst according to claim15 for hydrogenation reactions, dihydroxylation reactions, hydrolysisreactions, metathesis reactions, carbon-carbon bond formation reactions,hydroamination reactions, epoxidations, aziridinations, cycloadditions,hetero-Diels-Alder reactions, hetero-ene reactions, Claisenrearrangements, carbonyl reductions, sigmatropic rearrangements,additions of nucleophiles to π-bonds, addition of nucleophiles tocarbonyl groups and ring-opening reactions.
 20. The use of a supportedcatalyst according to claim 19 for hydrogenation reactions, hydrolysisreactions and carbon-carbon bond formation reactions.
 21. The use of asupported catalyst according to claim 19, wherein the catalyst isseparated from the reaction mixture, and re-used in subsequentreactions.
 22. The use of a supported catalyst according to claim 20,wherein the catalyst is separated from the reaction mixture, and re-usedin subsequent reactions.
 23. The use of a supported catalyst accordingto claim 21, wherein the catalyst is separated from the reactionmixture, and re-used in subsequent reactions.